Activated ERK1/2 threonine-phosphorylates FGFR3-associated FRS2.

Stable Identifier
R-HSA-5654565
Type
Reaction
Species
Homo sapiens
Compartment
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Summation

FRS2 has 8 canonical MAPK phosphorylation sites which are phosphorylated by activated ERK1/2 after FGF stimulation. Phosphorylation of these 8 threonine residues counteracts the activating effect of tyrosine phosphorylation of FRS2, although the exact mechanism for this negative regulation is not known. Expression of a version of FRS2 in which the 8 threonine residues are mutated to valine results in enhanced tyrosine phosphorylation of FRS2, enhanced GRB2-SOS1 recruitment and a more sustained MAPK response. The 8 threonine residues are not conserved in FRS3; as a result, signaling through FRS3 complexes do not appear to be subject to this downregulation.

Literature References
PubMed ID Title Journal Year
12974390 EGFR and FGFR signaling through FRS2 is subject to negative feedback control by ERK1/2

Wu, Y, Chen, Z, Ullrich, A

Biol Chem 2003
12419216 The docking protein FRS2alpha controls a MAP kinase-mediated negative feedback mechanism for signaling by FGF receptors

Lax, I, Wong, A, Lamothe, B, Lee, A, Frost, A, Hawes, J, Schlessinger, J

Mol Cell 2002
19652666 FGF-receptor substrate 2 functions as a molecular sensor integrating external regulatory signals into the FGF pathway

Zhou, W, Feng, X, Wu, Y, Benge, J, Zhang, Z, Chen, Z

Cell Res 2009
18452557 Regulation of growth factor signaling by FRS2 family docking/scaffold adaptor proteins

Gotoh, N

Cancer Sci 2008
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Participant Of
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Catalyst Activity
Title
MAP kinase activity of p-T,Y MAPK dimers [cytosol]
Physical Entity
Activity
Orthologous Events
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